Concerns related to adverse effects:• Hepatotoxicity: Acetaminophen may cause hepatic toxicity with acute overdose; in addition chronic daily dosing has resulted in liver damage in some adults. • Hypersensitivity: Discontinue use if hypersensitivity occurs.Disease-related concerns:• Ethanol use: Use with caution in patients with alcoholic liver disease; consuming ≥3 alcoholic drinks/day may increase the risk of liver damage.Special populations: • Pediatrics: Not for use in children <12 years of age.Other warnings/precautions:• Dosage limit: Limit acetaminophen dose to <4 g/day in adults.• Self-medication (OTC use): Should not be used with other products containing acetaminophen. Patients should be instructed to contact healthcare provider if new symptoms occur, if redness or swelling occurs, or pain lasting >10 days.

Interactions

Anticonvulsants (Hydantoin): May increase the metabolism of Acetaminophen. This may 1) diminish the effect of acetaminophen; and 2) increase the risk of liver damage. Risk C: Monitor therapyBarbiturates: May increase the metabolism of Acetaminophen. This may 1) diminish the effect of acetaminophen; and 2) increase the risk of liver damage. Risk C: Monitor therapyCarBAMazepine: May increase the metabolism of Acetaminophen. This may 1) diminish the effect of acetaminophen; and 2) increase the risk of liver damage. Risk C: Monitor therapyCholestyramine Resin: May decrease the absorption of Acetaminophen. Effect is minimal if cholestyramine is administered 1 hour after acetaminophen. Risk D: Consider therapy modificationConivaptan: May increase the serum concentration of CYP3A4 Substrates (Low risk). Risk C: Monitor therapyCyproterone: May decrease the serum concentration of CYP1A2 Substrates. Risk C: Monitor therapyCyproterone: May decrease the serum concentration of CYP2E1 Substrates. Risk C: Monitor therapyDasatinib: Acetaminophen may enhance the hepatotoxic effect of Dasatinib. Dasatinib may increase the serum concentration of Acetaminophen. Risk D: Consider therapy modificationImatinib: Acetaminophen may enhance the hepatotoxic effect of Imatinib. Imatinib may increase the serum concentration of Acetaminophen. Risk D: Consider therapy modificationIsoniazid: May enhance the adverse/toxic effect of Acetaminophen. Risk C: Monitor therapyMetyrapone: May increase the serum concentration of Acetaminophen. More importantly, by inhibiting the conjugative metabolism of acetaminophen, metyrapone may shift the metabolism towards the oxidative route that produces a hepatotoxic metabolite. Risk C: Monitor therapyPeginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates. Risk C: Monitor therapyProbenecid: May increase the serum concentration of Acetaminophen. Probenecid may also limit the formation of at least one major non-toxic metabolite, possibly increasing the potential for formation of the toxic NAPQI metabolite. Risk D: Consider therapy modificationSORAfenib: Acetaminophen may enhance the hepatotoxic effect of SORAfenib. SORAfenib may increase the serum concentration of Acetaminophen. Risk D: Consider therapy modificationTocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapyVitamin K Antagonists (eg, warfarin): Acetaminophen may enhance the anticoagulant effect of Vitamin K Antagonists. Most likely with daily acetaminophen doses >1.3 g for >1 week. Risk C: Monitor therapyEthanol/Nutrition/Herb Interactions Ethanol: Excessive intake of ethanol may increase the risk of acetaminophen-induced hepatotoxicity. Avoid ethanol or limit to <3 drinks/day.